Associations of persistent organic pollutants in human adipose tissue with retinoid levels and their relevance to the redox microenvironment.

Humans are exposed to a myriad of chemical substances in both occupational and environmental settings. Persistent organic pollutants (POPs) have drawn attention for their adverse effects including cancer and endocrine disruption. Herein, the objectives were 1) to describe serum and adipose tissue retinol levels, along with serum retinol binding protein 4 (RBP4) concentrations, and 2) to assess the associations of adipose tissue POP levels with these retinoid parameters, as well as their potential interaction with the previously-observed POP-related disruption of redox microenvironment.

In utero exposure to bisphenol-A disrupts key elements of retinoid system in male mice offspring.

The retinoid system controls essential cellular processes including mitosis, differentiation and metabolism among others. Although the retinoid-signalling pathway is a potential target for the action of several endocrine disrupting chemicals (EDCs), the information about the developmental effects of bisphenol-A (BPA) on the hepatic retinoid system is scarce. Herein, male mice were in utero exposed to BPA following maternal subcutaneous doses of 0, 10 and 100 μg/kg bw/day from gestational day 9-16 and they were sacrificed at post-natal day 30.

Comparative study on short- and long-term behavioral consequences of organophosphate exposure: relationship to AChE mRNA expression.

Organophosphates (OPs) affect behavior by inhibiting acetylcholinesterase (AChE). While the cognitive short-term effects may be directly attributed to this inhibition, the mechanisms that underlie OP's long-term cognitive effects remain controversial and poorly understood. Accordingly, two experiments were designed to assess the effects of OPs on cognition, and to ascertain whether both the short- and long-term effects of are AChE-dependent.

Chronic dietary exposure to chlorpyrifos causes behavioral impairments, low activity of brain membrane-bound acetylcholinesterase, and increased brain acetylcholinesterase-R mRNA.

Chlorpyrifos (CPF) is an organophosphate (OP) insecticide that is metabolically activated to the highly toxic chlorpyrifos oxon. Dietary exposure is the main route of intoxication for non-occupational exposures. However, only limited behavioral effects of chronic dietary exposure have been investigated.

Kinetics of inhibition of soluble peripheral nerve esterases by PMSF: a non-stable compound that potentiates the organophosphorus-induced delayed neurotoxicity.

The kinetic analysis of esterase inhibition by acylating compounds (organophosphorus carbamates and sulfonyl fluorides) is sometimes unable to yield consistent results by fitting simple inhibition kinetic models to experimental data of complex systems. In this work, kinetic data were obtained for phenylmethylsulfonyl fluoride (PMSF) tested at different concentrations incubated for up to 3 h with soluble fraction of chicken peripheral nerve. PMSF is a protease and esterase inhibitor causing protection or potentiation of the organophosphorus-induced delayed neuropathy and is unstable in water solution.

Inhibition with spontaneous reactivation of carboxyl esterases by organophosphorus compounds: paraoxon as a model.

In this work kinetic data were obtained for different paraoxon concentrations incubated with chicken serum and the soluble fraction of chicken peripheral nerve. A kinetic model equation was deduced by assuming a multienzymatic system with three different simultaneously occurring molecular phenomena: (1) inhibition; (2) simultaneous spontaneous reactivation; (3) "ongoing" inhibition (inhibition during the substrate reaction). A three-dimensional fit of the model was applied to analyze the experimental data versus the concentration of the inhibitor and the preincubation time in an inhibition experiment.

Inhibition with spontaneous reactivation and the "ongoing inhibition" effect of esterases by biotinylated organophosphorus compounds: S9B as a model.

The biotinylated organophosphorus compound 1-(saligenin cyclic phospho)-9-biotinyldiaminononane (S9B) has been used for the detection, labeling and isolation of the membrane-bound neuropathy target esterase (NTE) as it was considered a specific inhibitor of NTE. After incubation with the soluble fraction of chicken peripheral nerve, most of the soluble esterase activity was highly sensitive to S9B, indicating NTE-like esterases. A kinetic model equation was used to assume a multi-enzymatic system with three different simultaneously occurring molecular phenomena; (1) inhibition; (2) simultaneous spontaneous reactivation; and (3) ongoing inhibition (inhibition during the substrate reaction); to fit the data to analyze kinetic behavior.

Increase of R-/S-methadone enantiomer concentration ratio in serum of patients treated with either nevirapine or efavirenz.

An increased methadone enantiomer ratio (R/S) was associated to both nevirapine (179%, n=5) and efavirenz (36%, n=9) treatments when compared with that of controls (n=52). Additionally, in four follow-up patients, both R- and S-methadone normalized concentrations decreased (19%-93%) while R/S increased (22%-314%) following nevirapine/efavirenz treatment. R/S decreased (42%) after non-compliance with efavirenz treatment.

Detection of clinical interactions between methadone and anti-retroviral compounds using an enantioselective capillary electrophoresis for methadone analysis.

A capillary electrophoresis method was developed to detect interactions between methadone and anti-retroviral compounds. Eight subjects, who underwent methadone maintenance treatment in the Province of Alicante (Spain), consented to participate in the present study. Of those, one subject was followed up for 123 days to detect drug-drug interactions.

The inhibition of the high sensitive peripheral nerve soluble esterases by mipafox. A new mathematical processing for the kinetics of inhibition of esterases by organophosphorus compounds.

In the study of organophosphorus (OP) sensitive enzymes, careful discrimination of specific components within a complex multienzymatic mixture is needed. However, standard kinetic analysis gives inconsistent results (i.e.

[Prevalence of infection by HIV and hepatitis C virus in a cohort of patients on methadone treatment].

Background And Objectives: Methadone maintenance treatment reduces drug-related-harm. The aims of the study were: a) to analyze the temporal tendencies of prevalence of infection by HIV and hepatitis C virus, and b) to evaluate if the adherence to methadone maintenance treatment protects against the infection by HIV and hepatitis C virus.

Patients And Method: Retrospective longitudinal study with All the 1,487 patients receiving treatment in the Province of Alicante between June 1990 and December 1997.

Properties of phenyl valerate esterase activities from chicken serum are comparable with soluble esterases of peripheral nerves in relation with organophosphorus compounds inhibition.

Chicken serum, the usual in vivo animal for testing organophosphorus delayed neuropathy, has long been reported not to contain a homologous activity of the neuronal neuropathy target esterase (NTE) activity when it is assayed according to standard methods as the phenyl valerate esterase (PVase) activity, which is resistant to paraoxon and sensitive to mipafox. However, a PVase activity (1000-1500 nmol/min/ml) can be measured in serum that is extremely sensitive to both paraoxon, a non-neuropathic organophosphorus compound and mipafox, a model neuropathy inducer. The inhibition was time progressive in both cases, suggesting a covalent phosphorilating reaction.

Survival study of opioid addicts in relation to its adherence to methadone maintenance treatment.

Objectives: To study the putative role of methadone maintenance treatment in the improvement of life expectancy of opioid addicts.

Design: Retrospective longitudinal study.

Participants: All 1487 patients receiving methadone maintenance treatment in Alicante between June 1990 and December 1997.